Morphine treatment of rats has resulted in a transient rise in cyclic AMP in midbrain-thalamus. The anatomical location of the cyclic AMP change, the temporal correlation of the rise with the onset of analgesia, and preliminary indications that the rise is blocked by naloxone suggest that cyclic AMP may mediate the analgesia evoked by morphine. This project proposes a three-fold approach to the amplification of the original observations and the evaluation of the role cyclic AMP may have in morphine action: 1) The morphine dose relationship with analgesia response and with cyclic AMP response will be assessed. Analgesia and cyclic AMP will be measured in the same animals. 2) Generalizability of the biochemical change will be evaluated from measurements of responses following narcotic agonists and antagonists including naloxone, levorphanol, and dextrorphan. Association of a particular effect of morphine with the cyclic AMP change may be inferred on the basis of the differing pharmacological properties of the morphine analogs. 3) The anatomical location of the cyclic AMP change will be determined at the cellular level by immunohistofluorescence. Knowledge of the location of the cyclic AMP change may indicate which particular effect of morphine the cyclic AMP change is associated with and, further, may suggest a sequence of neural events participating in the acute action of morphine.